Project Summary/Abstract In obese children, excess fat exerts an unfavorable burden on the respiratory system, particularly during exercise. It is unclear if this burden reduces exercise tolerance, provokes dyspnea on exertion (DOE), or contributes to respiratory symptoms, which could be misdiagnosed as asthma. Obesity-related respiratory symptoms are wrongly labeled asthma in over 50% of cases placing obese children at risk of unnecessary treatment and potentially a reluctance to exercise, which is counterproductive to weight loss. We propose that most of the respiratory effects in obese children are the result of low lung volume breathing, i.e., a reduction in functional residual capacity at rest, and end-expiratory lung volume during exercise. It is also unclear whether moderate weight loss and regular exercise make a significant change in respiratory function, exercise tolerance, or DOE in obese children. This is not to imply that weight loss and regular exercise are not important in the treatment of childhood obesity, but it is unclear if this conventional prescription of modest weight loss and regular exercise yields significant changes in respiratory function, exercise tolerance, and/or DOE in obese children. Conversely, the effects of continued weight gain on respiratory function, exercise tolerance, and DOE are also unknown. The overall objective of this application is to investigate the respiratory effects of obesity in prepubescent children, including obese children with respiratory symptoms misdiagnosed as asthma, before and after 1) a program of weight loss and regular exercise and 2) continued weight gain as compared with normal weight children before and after 1 yr. Our approach will be to examine respiratory function, exercise tolerance, and DOE in prepubescent obese boys and girls (Tanner score?3, 8-12 yr), including those misdiagnosed with asthma, before and after 1) weight loss and regular exercise and 2) continued weight gain as compared with prepubescent normal weight boys and girls before and after a control period of 1 yr. We will test the following hypotheses in obese children as compared with normal weight children. Aim 1) Obesity will decrease respiratory function but to a greater extent in obese children misdiagnosed with asthma. Aim 2) Obesity will decrease exercise tolerance but not cardiorespiratory fitness, except in obese children misdiagnosed with asthma where both may be reduced. Aim 3) Obesity will increase DOE but to a greater extent in obese children misdiagnosed with asthma. Aim 4) Weight loss and regular exercise will improve respiratory function, exercise tolerance, and DOE in obese children, including those misdiagnosed with asthma, while continued weight gain will worsen respiratory function, exercise tolerance, and DOE in obese children, including those misdiagnosed with asthma, as compared with normal weight children before and after 1 yr. These results will have broad and immediate clinical impact on the care of obese children, especially those with respiratory symptoms misdiagnosed as asthma.